Recently, reasonable correlations have been drawn between the clinical presence of chronic obstructive pulmonary disease and the homozygous absence of alpha 1-antitrypsin in serum. Moreover, papain and ill-defined white cell extracts have produced chronic obstructive pulmonary disease in animals. We would like to demonstrate that one, well-characterized, enzyme in leukocyte lysosomes can produce experimental chronic obstructive pulmonary disease. This study will explore whether a neutral protease of leukocyte lysosomes can provoke the lesions of chronic obstructive pulmonary disease in animals, and to study the activity of this enzyme or its inhibitor in the peripheral blood leukocytes of patients with chronic obstructive pulmonary disease. Normal human subjects will be screened for the presence of neutral protease in lysosomes of PMN's of peripheral blood. We will also establish the presence and concentration of its specific, cytoplasmic inhibitor. The strategy behind these experiments is that it is entirely possible that there exists a population of patients with chronic obstructive pulmonary disease in whom disease is not due to insufficient inhibition of leukoprotease by serum alpha l-antitrypsin but due to the lack of a cytoplasmic inhibitor of the lysosomal enzyme. Should we find that there are clinical conditions associated with absence of this intracellular inhibitor we shall do genetic studies using subjects with the deficit as probands. Another part of the protocol describes studies in rats which will be treated with leukocyte lysosomal poteases prepared from rat, human and rabbit peripheral blood leukocytes. Groups will be treated with each of these enzyme preparations before and after admixture of cytoplasmic inhibitor sufficient to neutralize the protease activity. Should it prove possible to produce histologic changes resembling chronic obstructive pulmonary disease by both papain and lysosomal proteases, it will be possible to determine whether the inhibitor administered either intertracheally or systemically has the capacity to avert these changes. The strategy behind these experiments is that it should be possible to produce changes resembling chronic obstructive pulmonary diseases by means of a purified, isolated, lysosomal protease prepared from the leukocytes of various species. Should this prove possible, then all our previous work on mechanisms of lysosomal en (Text Truncated - Exceeds Capacity)